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20-Hydroxyecdysone (20E) is an arthropod steroid hormone that possesses a number of beneficial pharmacological activities in humans, including anabolic, antioxidant, hypoglycemic, cardioprotective, hepatoprotective, neuroprotective, and antineoplastic properties, etc. While several studies have explored the anabolic activity of 20E in muscle cells, they have concentrated on its effects on myofibril size, protein biosynthesis intensity, and myostatin expression, without assessing energy metabolism. In this research, we have demonstrated that 20E boosts both catabolism and anabolism, coupling energy-producing and biosynthetic metabolic processes in mouse myoblasts and fibroblasts in the same way. Using a transcriptomic approach, we identified the 20E-mediated up-regulation of genes involved in different metabolic processes. Further experiments revealed that 20E increased the levels of enzymes involved in glycolysis and one-carbon metabolism. It also increased the uptake of glucose, glycolysis, respiration, the production of ATP, and global protein biosynthesis in mouse myoblasts and fibroblasts. This phenomenon involves the PI3K/AKT/mTOR signaling pathway. Taken together, the observed 20E-dependent upregulation of energy metabolism may be the main reason for 20E’s well-known anabolic activity.

The midface is a key area in facial aesthetics, highly susceptible to age-related changes such as fat pad absorption, bone resorption, and loss of skin elasticity. These changes lead to the formation of prominent folds, such as the nasolabial fold. In addition, critical vascular structures and non-vascular components, such as the facial artery, angular artery, and parotid gland, make this region prone to complications during filler injections. High-frequency ultrasound (HFUS) offers real-time, radiation-free visualization of facial anatomy, enabling injectors to accurately target the desired treatment planes and avoid critical structures. This article is the second in a series of articles on ultrasound-guided facial injections and focuses on the midface. It provides a detailed overview of the sonographic anatomy of key areas, including the nose, tear trough, nasolabial fold, zygomatic, and preauricular regions. Step-by-step techniques for ultrasound-guided filler injections are described, emphasizing the importance of scanning both before and during injections to ensure safe filler placement. By using ultrasound in this area, injectors can possibly minimize risks such as vascular occlusion and other complications, such as the Tyndall effect and intra-parotid injection. With ongoing advancements, ultrasound-guided injections are expected to become more refined, enhancing both aesthetic outcomes and patient safety.

Ongoing outbreaks and often rapid spread of infections caused by coronaviruses, influenza, Nipah, Dengue, Marburg, monkeypox, and other viruses are a concern for health authorities in most countries. Therefore, the search for and study of new antiviral compounds are in great demand today. Since almost all viruses with pandemic potential have immunotoxic properties of various origins, particular attention is paid to the search and development of immunomodulatory drugs. We have synthesised a new compound related to indole-3-carboxylic acid derivatives (hereinafter referred to as the XXV) that has antiviral and interferon-inducing activity. The purpose of this work is to study the effect of the XXV on the stimulation of the expression of toll-like receptor genes, interferons, and immunoregulatory cytokines in a macrophage-like cell model. In this study, real-time PCR methods were used to obtain data on the transcriptional activity of genes in macrophage-like cells. Stimulation of the genes of toll-like receptors TLR2, TLR3, TLR4, TLR7, TLR8, and TLR9 was detected. A high-fold increase in stimulation (from 6.5 to 16,000) of the expression of the TLR3 and TLR4 genes was detected after 4 h of exposure to the XXV. Increased activity of interferon (IFNA1, IFNA2, IFNB1, IFNK, and IFNλ1) genes with simultaneous stimulation of the expression of interferon receptor (IFNAR1 and IFNAR2) genes and signalling molecule (JAK1 and ISG15) genes was detected. Increased fold stimulation of the expression of the cytokine genes IL6, TNFA, IL12A, and IL12B was also observed. Thus, it is shown that the XXV is an activator of TLR genes of innate immunity, which trigger signalling mechanisms of pathogen “recognition” and lead to stimulation of the expression of genes of proinflammatory cytokines and interferons.

A limestone relief fragment with a figure in a winged disk from the fifth-century BCE Hall of 100 Columns at Persepolis in southwestern Iran that entered the Harvard Art Museums’ collections in 1943 preserves significant traces of its original coloration and has played a key role in the rediscovery of polychromy at the Achaemenid Persian capital. After tracing the fragment’s journey to Cambridge, MA, this article presents the results of recent technical studies of its pigment remains, including visible light-induced infrared luminescence (VIL) imaging, X-ray fluorescence (XRF) spectroscopy, and the analysis of micro samples by Raman spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM), and polarizing light microscopy (PLM). The new scientific data is compared to the findings of ongoing investigations of polychromies at Persepolis and other Achaemenid Persian sites and evaluated for the information it can and cannot provide on the original appearance of the figure in the winged disk, likely the Zoroastrian god Ahuramazda. The article reviews past attempts at reconstructing the relief’s coloration and the assumptions that guided them, recounts the experience of creating a tangible three-dimensional color reconstruction for an exhibition, and concludes with some general thoughts on the valuation of colorfulness.

Analysis of the white blood cell differential as part of a flow cytometry-based approach is a common routine diagnostic tool used in clinics and research. For human blood, the methodological approach, suitable markers, and gating strategies are well-established. However, there is a lack of information regarding the mouse blood count. In this article, we deliver a fast and easy protocol for reprocessing mouse blood for the purpose of flow cytometric analysis, as well as suitable markers and gating strategies. We also present two possible applications: for the analysis of the whole blood count, with blood from a cardiac puncture, and for the analysis of a certain leukocyte subset at multiple time points in the framework of a mouse experiment, using blood from the facial vein. Additionally, we provide orientation values by applying the method to 3-month-old and 24-month-old male and female C57BL/6J mice. Our analyses demonstrate differences in the leukocyte fractions depending on age and sex. We discuss the influencing factors and limitations that can affect the results and that, therefore, need to be considered when applying this method. The present study fills the gap in the knowledge related to the rare information on flow cytometric analysis of mouse blood and, thus, lays the foundation for further investigations in this area.

Background: Cardiovascular diseases (CVDs) represent major medical and socio-economic challenges worldwide. There is substantial evidence that CVD is closely linked to inflammatory changes triggered by a complex cytokine network. In this context, interleukin 10 (IL-10) plays an important role as a pleiotropic cytokine with an anti-inflammatory capacity. In this study (a substudy of ClinTrials.gov, identifier: NCT01045070), the prognostic relevance of IL-10 levels and IL-10 haplotypes (rs1800896/rs1800871/rs1800872) was assessed regarding adverse cardiovascular outcomes (combined endpoint: myocardial infarction, stroke/transient ischemic attack, cardiac death and death according to stroke) within a 10-year follow-up. Patients and methods: At baseline, 1002 in-patients with CVD were enrolled. Serum levels of IL-10 were evaluated utilizing flow cytometry (BD™ Cytometric Bead Array). Haplotype analyses were carried out by polymerase chain reactions with sequence-specific primers (PCR-SSP). Results: In a survival analysis, IL-10 haplotypes were not proven to be cardiovascular prognostic factors in a 10-year follow-up (Breslow test: p = 0.423). However, a higher IL-10 level was associated with adverse cardiovascular outcomes (Breslow test: p = 0.047). A survival analysis considering adjusted hazard ratios (HRs) could not confirm this correlation (Cox regression: adjusted HR = 1.26, p = 0.168). Conclusion: In the present study, an elevated IL-10 level but not IL-10 haplotypes was linked to adverse cardiovascular outcomes (10-year follow-up) in a cohort of CVD patients.

The demand for high-strength aluminum alloys for the laser powder bed fusion (LPBF) process is still growing. However, to date, the crack susceptibility of conventional alloys as well as the high prices for specially developed alloys are the main obstacles for the use of high-strength aluminum alloys for LPBF. In this paper, crack-free LPBF samples with a relative density >99.9% were processed from AlMgSi1Zr (6182 series alloy) powder, to which 0.5 wt.-% Zr and 0.5 wt.-% Ti were added via mechanical mixing. No hot cracks were found in the µCT scans. Moreover, a fully equiaxed microstructure with a mean size of the α-Al grains of 1.2 µm was observed in the as-built parts. Al3(Zr,Ti) particles were observed, acting as efficient heterogeneous grain refiners for α-Al by building a semi-coherent interface. Unmolten Ti and Zr particles with sizes up to 80 µm were found in the α-Al phase. The resulting fine-grained microstructure led to a tensile strength of 329 ± 4 MPa and a total elongation at a break of 11.4 ± 0.9% after solution heat treatment, quenching in water, and subsequent artificial ageing.

In 2022/2023, Europe experienced its third consecutive season of high-pathogenicity avian influenza. During this period, the Czech Republic was again severely affected. For the first time, the number of culled birds approached one million, which was three times higher than in previous seasons. In parallel to the outbreaks in poultry, mass die-offs of gulls were also observed. In the present study, we performed whole-genome sequencing and phylogenetic analysis of 137 H5N1 strains collected in the Czech Republic in 2022/2023 (94.6% of all outbreaks or locations). The analysis revealed four distinct genotypes: AB, CH, BB and AF. Phylogenetic analysis suggested that the AF genotype persisted from the previous H5N1 season without reassortment. In addition, the genotype BB, which was detected mainly in gulls, showed a noticeable strain diversity at the local level. This virus was also responsible for a single outbreak in commercially bred turkeys. Finally, an interesting spatio-temporal cluster with three co-circulating H5N1 genotypes, AB, CH and AF, was identified with no evidence of intrasubtype reassortment. Highly sensitive molecular surveillance and the timely sharing of genomic sequences and associated metadata could greatly assist in tracking the spread and detecting molecular changes associated with the increased virulence of this potentially zoonotic pathogen.

Bimetallic nanoparticles (BMNPs) combine unique and synergistic properties of two metals, allowing new specific applications. In this study, bimetallic AuFe nanoparticles and their conjugates with methotrexate (MTX) were obtained with an environmentally safe method of metal-vapor synthesis. The composition and electronic structure of the particles were investigated with X-ray photoelectron spectroscopy (XPS), energy dispersive X-ray (EDX) spectrum and X-ray absorption spectroscopy (XANES and EXAFS). The effects of BMNP-MTX conjugates on human primary cells and tumor cell lines were evaluated with neutral red uptake and MTT in vitro cytotoxicity assays. Bright-field microscopy analyses of tumor spheroid size and evaluations of tumor spheroid vitality based on SFDA AM staining were carried out. In vitro assays for an antibacterial activity evaluation of the generated samples were performed. The influence of BMNP-MTX on cytokine production with normal leukocytes was assessed using ELISA. X-ray analyses of the samples demonstrated that gold was in the ground state Au0 as well as Au+ and Au3+ states are present in small quantities, whereas iron existed as a mixture of non-histometric oxides with states close to Fe2+ and Fe3+. The modification of the AuFe system with MTX is accompanied by a threefold increase in the relative proportion of the Au+ state. BMNP-MTX conjugates demonstrated significant antitumor activity compared to the drug alone, which proves the ability of the generated nanoconjugates to improve the effectiveness of MTX therapy. This was confirmed by a marked reduction in the size and vitality of AuFe-MTX-treated 3D tumor spheroids. In addition to their selective antitumor activity, AuFe-MTX exhibited moderate antibacterial activity and induced sample-specific cytokine production with normal human leukocytes—which points to an immunostimulatory potential. The present findings indicate important and diverse biological properties of BMNP-MTX conjugates and thus highlight perspectives for their biomedical applications and new immune-specific abilities.

A class of controlled objects is considered, the dynamics of which are determined by a vector system of ordinary differential equations with a partially known right-hand side. It is presumed that the state variables and their velocities can be measured. Designing a robust tracking controller under some constraints to admissible state variables is the research goal. This construction, which extends the results for the average subgradient technique (ASG), and is an update of the subgradient descent technique (SDM) and integral sliding mode (ISM) approach, is realized by using the Legendre–Fenchel transform. A two-link robot manipulator with three revolute joints, powered by individual PMDC motors, is presented as an illustrative example of the suggested approach implementation.

The rapid evolution of new SARS-CoV-2 variants poses a continuing threat to human health. Vaccination has become the primary therapeutic intervention. The goal of the current work was the construction of immunogenic virus-like particles (VLPs). Here, we describe a human cell line for cost-efficient and scalable production of immunogenic SARS-CoV-2 VLPs. The modular design of the VLP-production platform facilitates rapid adaptation to new variants. Methods: The N, M-, and E-protein genes were integrated into the genome of Expi293 cells (ExpiVLP_MEN). Subsequently, this cell line was further modified for the constitutive expression of the SARS-CoV-2 spike protein. The resulting cell line (ExpiVLP_SMEN) released SARS-CoV-2 VLP upon exposure to doxycycline. ExpiVLP_SMEN cells were readily adapted for VLP production in a 5 L bioreactor. Purified VLPs were quantified by Western blot, ELISA, and nanoparticle tracking analysis and visualized by electron microscopy. Immunogenicity was tested in mice. Results: The generated VLPs contained all four structural proteins, are within the size range of authentic SARS-CoV-2 virus particles, and reacted strongly and specifically with immunoserum from naturally infected individuals. The VLPs were stable in suspension at 4 °C for at least 10 weeks. Mice immunized with VLPs developed neutralizing antibodies against lentiviruses pseudotyped with the SARS-CoV-2 spike protein. The flexibility of the VLP-production platform was demonstrated by the rapid switch of the spike protein to a new variant of concern (BA.1/Omicron). The present study describes an efficient, scalable, and adaptable production method of immunogenic SARS-CoV-2 VLPs with therapeutic potential.

The results of modifying the surface of austenitic stainless steel by anodic plasma electrolytic treatment are presented. Surface treatment was carried out in aqueous electrolytes based on ammonium chloride (10%) with the addition of ammonia (5%) as a source of nitrogen (for nitriding), boric acid (3%) as a source of boron (for boriding) or glycerin (10%) as a carbon source (for carburizing). Morphology, surface roughness, phase composition and microhardness of the diffusion layers in addition to the tribological properties were studied. The influence of physicochemical processes during the anodic treatment of the features of the formation of the modified surface and its operational properties are shown. The study revealed the smoothing of irregularities and the reduction in surface roughness during anodic plasma electrolytic treatment due to electrochemical dissolution. An increase in the hardness of the nitrided layers to 1450 HV with a thickness of up to 20–25 μm was found due to the formation of iron nitrides and iron-chromium carbides with a 3.7-fold decrease in roughness accompanied by an increase in wear resistance by 2 orders. The carburizing of the steel surface leads to a smaller increase in hardness (up to 700 HV) but a greater thickness of the hardened layer (up to 80 μm) due to the formation of chromium carbides and a solid solution of carbon. The roughness and wear resistance of the carburized surface change are approximately the same values as after nitriding. As a result of the boriding of the austenitic stainless steel, there is no hardening of the surface, but, at the same time, there is a decrease in roughness and an increase in wear resistance on the surface. It has been established that frictional bonds in the friction process are destroyed after all types of processing as a result of the plastic displacement of the counter body material. The type of wear can be characterized as fatigue wear with boundary friction and plastic contact. The correlation of the friction coefficient with the Kragelsky–Kombalov criterion, a generalized dimensionless criterion of surface roughness, is shown.

New hybrid materials based on Ag nanoparticles stabilized by a polyaminopropylalkoxysiloxane hyperbranched polymer matrix were prepared. The Ag nanoparticles were synthesized in 2-propanol by metal vapor synthesis (MVS) and incorporated into the polymer matrix using metal-containing organosol. MVS is based on the interaction of extremely reactive atomic metals formed by evaporation in high vacuum (10−4–10−5 Torr) with organic substances during their co-condensation on the cooled walls of a reaction vessel. Polyaminopropylsiloxanes with hyperbranched molecular architectures were obtained in the process of heterofunctional polycondensation of the corresponding AB2-type monosodiumoxoorganodialkoxysilanes derived from the commercially available aminopropyltrialkoxysilanes. The nanocomposites were characterized using transmission (TEM) and scanning (SEM) electron microscopy, X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (PXRD) and Fourier-transform infrared spectroscopy (FTIR). TEM images show that Ag nanoparticles stabilized in the polymer matrix have an average size of 5.3 nm. In the Ag-containing composite, the metal nanoparticles have a “core-shell” structure, in which the “core” and “shell” represent the M0 and Mδ+ states, respectively. Nanocomposites based on silver nanoparticles stabilized with amine-containing polyorganosiloxane polymers showed antimicrobial activity against Bacillus subtilis and Escherichia coli.

Heteronuclear diatomic rare gas molecular cations feature excited electronic terms with charge transfer character located several eV above the ground term. The role of such terms in collisions involving heteronuclear ions is studied theoretically under conditions typical of the plasma-based sources of UV and IR radiation. Calculations were carried out for processes of dissociative excitation, dissociative recombination and electron impact bound–bound excitation in Ar/Xe and Kr/Xe plasmas using the recently developed semiclassical approach combined with the ab initio data for potential energy curves and oscillator strengths of electronic transitions. The approach consistently describes the contributions from the entire rovibrational manifold to the processes studied. The cross sections of the processes mentioned are calculated for wide ranges of gas temperatures and electron energies. We show that the processes considered are quite effective when they are accompanied by transitions to charge transfer terms. For the range of electron energies typical of active media of UV and IR radiation sources the cross sections exceed those reported for the processes usually considered to involve transitions between the ground and first excited electronic state. The excitation of charge transfer electronic terms can play an important role in the kinetics of rare gas mixture plasmas.

In 2021/2022, the re-emergence of highly pathogenic avian influenza (HPAI) occurred in Europe. The outbreak was seeded from two sources: resident and reintroduced viruses, which is unprecedented in the recorded history of avian influenza. The dominant subtype was H5N1, which replaced the H5N8 subtype that had predominated in previous seasons. In this study, we present a whole genome sequence and a phylogenetic analysis of 57 H5N1 HPAI and two low pathogenic avian influenza (LPAI) H5N1 strains collected in the Czech Republic during 2021/2022. Phylogenetic analysis revealed close relationships between H5N1 genomes from poultry and wild birds and secondary transmission in commercial geese. The genotyping showed considerable genetic heterogeneity among Czech H5N1 viruses, with six different HPAI genotypes, three of which were apparently unique. In addition, second-order reassortment relationships were observed with the direct involvement of co-circulating H5N1 LPAI strains. The genetic distance between Czech H5N1 HPAI and the closest LPAI segments available in the database illustrates the profound gaps in our knowledge of circulating LPAI strains. The changing dynamics of HPAI in the wild may increase the likelihood of future HPAI outbreaks and present new challenges in poultry management, biosecurity, and surveillance.

In this study, a lumped parameter model, developed and extensively validated by the authors, is used to simulate the impact of three different dehumidification technologies (mechanical refrigeration dehumidifier, liquid desiccant dehumidifier, and a heat recovery ventilation unit), at a commercial greenhouse growing potted roses in southwestern Ontario, Canada. Typical meteorological year (TMY) data from nearby Vineland, Ontario was used to provide the external weather data used in the model. Each greenhouse bay containing a dehumidification unit was simulated for spring, fall, and winter conditions. The potential reductions in energy use (kWh), greenhouse gas emissions (kg CO2e), and operating cost were estimated for each test case. The potential energy savings from switching from high-pressure sodium (HPS) to light-emitting diode (LED) lights were also examined. The simulation results showed that switching to LED lamps could reduce the electrical energy usage by up to 60% but would increase the space heating requirements. The expected energy-savings from using dehumidification equipment and switching from HPS to LED lighting in Canadian greenhouses is underrepresented in the literature. With the industry growing in the region, this study provides insight into the expected impact that these systems will have on the energy use in commercial greenhouses.

An extraction of significant information from Internet sources is an important task of pharmacovigilance due to the need for post-clinical drugs monitoring. This research considers the task of end-to-end recognition of pharmaceutically significant named entities and their relations in texts in natural language. The meaning of “end-to-end” is that both of the tasks are performed within a single process on the “raw” text without annotation. The study is based on the current version of the Russian Drug Review Corpus—a dataset of 3800 review texts from the Russian segment of the Internet. Currently, this is the only corpus in the Russian language appropriate for research of the mentioned type. We estimated the accuracy of the recognition of the pharmaceutically significant entities and their relations in two approaches based on neural-network language models. The first core approach is to sequentially solve tasks of named-entities recognition and relation extraction (the sequential approach). The second one solves both tasks simultaneously with a single neural network (the joint approach). The study includes a comparison of both approaches, along with the hyperparameters selection to maximize resulting accuracy. It is shown that both approaches solve the target task at the same level of accuracy: 52–53% macro-averaged F1-score, which is the current level of accuracy for “end-to-end” tasks on the Russian language. Additionally, the paper presents the results for English open datasets ADE and DDI based on the joint approach, and hyperparameter selection for the modern domain-specific language models. The result is that the achieved accuracies of 84.2% (ADE) and 73.3% (DDI) are comparable or better than other published results for the datasets.

Herein, we present our findings of an early appearance of the Monkeypox virus in Prague, Czech Republic. A retrospective analysis of biological samples, carried out on the 28th of April, revealed a previously unrecognized case of Monkeypox virus (MPxV) infection. Subsequent data analysis confirmed that the virus strain belongs to the ongoing outbreak. Combined with clinical and epidemiological investigations, we extended the roots of the current outbreak at least back to 16th of April, 2022.

In 2020–2021, the second massive dissemination of a highly pathogenic avian influenza of the H5Nx subtype occurred in Europe. During this period, the virus caused numerous outbreaks in poultry, including in the Czech Republic. In the present study, we provide an insight into the genetic variability of the Czech/2021 (CZE/2021) H5N8 viruses to determine the relationships between strains from wild and domestic poultry and to infer transmission routes between the affected flocks of commercial poultry. For this purpose, whole genome sequencing and phylogenetic analysis of 70 H5N8 genomes representing 79.7% of the cases were performed. All CZE/2021 H5N8 viruses belonged to the 2.3.4.4b H5 lineage and circulated without reassortment, retaining the A/chicken/Iraq/1/2020 H5N8-like genotype constellation. Phylogenetic analysis suggested the frequent local transmission of H5N8 from wild birds to backyard poultry and extensive spread among commercial poultry farms. In addition, the analysis suggested one cross-border transmission event. Indirect transmission via contaminated materials was considered the most likely source of infection. Improved biosecurity and increased collaboration between field veterinarians and the laboratory are essential to limit the local spread of the virus and to reveal and interrupt critical routes of infection.

Anaerobic digestion of animal manure is a potential bioenergy resource that avoids greenhouse gas emissions. However, the conventional approach is to use continuously stirred tank reactors (CSTRs) with hydraulic retention times (HRTs) of greater than 30 d. Reactors with biomass retention were investigated in this study in order to increase the efficiency of the digestion process. Filtered pig slurry was used as a substrate in an expanded granular sludge bed (EGSB) reactor and fixed-bed (FB) reactor. The highest degradation efficiency (ηCOD) and methane yield (MY) relative to the chemical oxygen demand (COD) were observed at the minimum loading rates, with MY = 262 L/kgCOD and ηCOD = 73% for the FB reactor and MY = 292 L/kgCOD and ηCOD = 76% for the EGSB reactor. The highest daily methane production rate (MPR) was observed at the maximum loading rate, with MPR = 3.00 m3/m3/d at HRT = 2 d for the FB reactor and MPR = 2.16 m3/m3/d at HRT = 3 d for the EGSB reactor. For both reactors, a reduction in HRT was possible compared to conventionally driven CSTRs, with the EGSB reactor offering a higher methane yield and production rate at a shorter HRT.

The paper presents the full-size Russian corpus of Internet users’ reviews on medicines with complex named entity recognition (NER) labeling of pharmaceutically relevant entities. We evaluate the accuracy levels reached on this corpus by a set of advanced deep learning neural networks for extracting mentions of these entities. The corpus markup includes mentions of the following entities: medication (33,005 mentions), adverse drug reaction (1778), disease (17,403), and note (4490). Two of them—medication and disease—include a set of attributes. A part of the corpus has a coreference annotation with 1560 coreference chains in 300 documents. A multi-label model based on a language model and a set of features has been developed for recognizing entities of the presented corpus. We analyze how the choice of different model components affects the entity recognition accuracy. Those components include methods for vector representation of words, types of language models pre-trained for the Russian language, ways of text normalization, and other pre-processing methods. The sufficient size of our corpus allows us to study the effects of particularities of annotation and entity balancing. We compare our corpus to existing ones by the occurrences of entities of different types and show that balancing the corpus by the number of texts with and without adverse drug event (ADR) mentions improves the ADR recognition accuracy with no notable decline in the accuracy of detecting entities of other types. As a result, the state of the art for the pharmacological entity extraction task for the Russian language is established on a full-size labeled corpus. For the ADR entity type, the accuracy achieved is 61.1% by the F1-exact metric, which is on par with the accuracy level for other language corpora with similar characteristics and ADR representativeness. The accuracy of the coreference relation extraction evaluated on our corpus is 71%, which is higher than the results achieved on the other Russian-language corpora.

Dengue is the most significant arbovirus worldwide and a public health threat to non-endemic areas in which Aedes vectors are present. Autochthonous dengue transmission has been reported in several European countries in the last decade. Infected travelers from endemic regions arriving to areas colonized by Aedes albopictus in Europe need to be monitored in surveillance and control programs. We aimed to perform molecular characterization of RT-PCR-positive dengue cases detected in Catalonia, northeastern Spain, from 2013 to 2018. The basic demographic information and the geographical regions of importation were also analyzed. One-hundred four dengue cases were studied (103 imported infections and the first autochthonous case in our region). The dengue virus strains detected were serotyped and genotyped using molecular methods, and phylogenetic analyses were conducted. All four dengue serotypes were detected in travelers, including up to 10 different genotypes, reflecting the global circulation of dengue in endemic areas. The primary travel-related case of the 2018 autochthonous transmission was not identified, but the molecular analysis revealed dengue serotype 1, genotype I of Asian origin. Our results highlight the diversity of imported dengue virus strains and the role of molecular epidemiology in supporting arbovirus surveillance programs.

The paper presents the preparation and characterization of novel composite materials based on microcrystalline cellulose (MCC) with silver nanoparticles (Ag NPs) in powder and gel forms. We use a promising synthetic conception to form the novel composite biomaterials. At first MCC was modified with colloidal solution of Ag NPs in isopropyl alcohol prepared via metal vapor synthesis. Then Ag-containing MCC powder was used as precursor for further preparation of the gels. The hydrogels were prepared by dissolving pristine MCC and MCC-based composite at low temperatures in aqueous alkali solution and gelation at elevated temperature. To prepare aerogels the drying in supercritical carbon dioxide was implemented. The as-prepared cellulose composites were characterized in terms of morphology, structure, and phase composition. Since many functional properties, including biological activity, in metal-composites are determined by the nature of the metal-to-polymer matrix interaction, the electronic state of the metal was carefully studied. The studied cellulose-based materials containing biologically active Ag NPs may be of interest for use as wound healing or water-purification materials.

The use of assisted reproductive technologies (ART) for the treatment of infertility is gaining popularity. Limited data on the overall vascular health of females with history of ART are available. This pilot study aimed to investigate the overall vascular health of females with history of ART compared to individuals who conceived spontaneously. The assessment of overall vascular health included the measurement of brachial blood pressure, central blood pressure, and pulse wave velocity, as well as the evaluation of the arterial stiffness and carotid intima-media thickness (cIMT) of the common carotid arteries. Conventional blood lipids including lipoprotein a (Lp(a)) were also determined. In total, 45 females with history of ART and 52 females who conceived spontaneously were included (mean age: 47.72 ± 5.96 years vs. 46.84 ± 7.43 years, p = 0.525). An initial comparison revealed a significantly higher prevalence of elevated Lp(a) in ART females ( p = 0.011). However, after multiple comparison correction, the significant result disappeared ( p = 0.132). Within the cohort of ART females, no significantly higher cardiovascular risk was detected regarding vascular function. The potentially higher prevalence of elevated Lp(a) in ART females must be further investigated in future studies, as it might contribute to the impaired reproductive process in this cohort.

(1) Background: Cardiorespiratory fitness (CRF) is known to be a prognostic factor regarding long-term morbidity and mortality. This study aimed to develop a standardized Stair Climbing Test (SCT) with a reliable correlation to spiroergometry and the 6MWT which can be used in healthy children as well as patients with congenital heart disease (CHD) and a restricted exercise capacity. (2) Methods: A total of 28 healthy participants aged 10-18 years were included. We tested the individuals' CRF by cardiopulmonary exercise testing (CPET) on a treadmill, the 6MWT, and a newly developed Stair Climbing Test (SCT). For the SCT, we defined a standardized SCT protocol with a total height of 13.14 m to achieve maximal exercise effects while recording time and vital parameters. To compare the SCT, the 6 Min Walking Test, and CPET, we introduced an SCT-Index that included patient data (weight, height) and time. To assess the SCT's feasibility for clinical practice, we also tested our protocol with five adolescents with complex congenital heart disease (i.e., Fontan circulation). (3) Results: A strong correlation was observed between SCT-Index and O 2 pulse (r = 0.921; p < 0.001). In addition, when comparing the time achieved during SCT (tSCT) with VO 2 max (mL/min/kg) and VO 2 max (mL/min), strong correlations were found (r = -0.672; p < 0.001 and r = -0.764; p < 0.001). Finally, we determined a very strong correlation between SCT-Index and VO 2 max (mL/min) (r = 0.927; p = <0.001). When comparing the 6MWD to tSCT, there was a moderate correlation (r = -0.544; p = 0.003). It appears to be feasible in patients with Fontan circulation. (4) Conclusions: We were able to demonstrate that there is a significant correlation between our standardized SCT and treadmill CPET. Therefore, we can say that the SCT can be used as an easy supplement to CPET and in certain contexts, it can also be used as a screening tool when CPET is not available. The advantages would be that the SCT is a simple, quick, cost-effective, and reliable standardized (sub)maximal exercise test to evaluate CRF in healthy children on a routine basis. We can even assume that it can be used in patients with congenital heart disease.

Arterial stiffness has received increasing interest as a cardiovascular marker in patients with aortic valve stenosis (AS). So far, studies on the impact of aortic valve replacement (AVR) on arterial stiffness have been equivocal. Two-dimensional speckle tracking (2DST) is a novel, non-invasive method to measure the motion of the vessel wall. In this prospective observational study, we aimed to assess the change in arterial stiffness of the common carotid artery (CCA) measured by 2DST in patients undergoing transcatheter aortic valve implantation (TAVI). A total of 47 patients were included in the study (age 80.04 ± 6.065 years). Peak circumferential strain (CS) was significantly improved after TAVI (4.50 ± 2.292 vs. 5.12 ± 2.958, p = 0.012), as was the peak strain rate (CSR) (0.85 ± 0.567 vs. 1.35 ± 0.710, p = 0.002). Body mass index (BMI), mean arterial pressure (MAP) and hemodynamic parameters were associated with this change. 2DST results did not correlate with aortic pulse wave velocity (aPWV) or augmentation index normalized to heart rate (AIx@75), suggesting a distinct difference between arterial stiffness of the CCA and other stiffness parameters. 2DST seems to be a promising new tool to assess arterial stiffness in TAVI patients.

Tuberculosis (TB) remains the second leading cause of death globally from a single infectious agent, and there is a critical need to develop improved imaging biomarkers and aid rapid assessments of responses to therapy. We aimed to utilize radiomics, a rapidly developing image analysis tool, to develop a scoring system for this purpose. A chest X-ray radiomics score (RadScore) was developed by implementing a unique segmentation method, followed by feature extraction and parameter map construction. Signature parameter maps that showed a high correlation to lung pathology were consolidated into four frequency bins to obtain the RadScore. A clinical score (TBscore) and a radiological score (RLscore) were also developed based on existing scoring algorithms. The correlation between the change in the three scores, calculated from serial X-rays taken while patients received TB therapy, was evaluated using Spearman's correlation. Poor correlations were observed between the changes in the TBscore and the RLscore (0.09 ( p -value = 0.36)) and the TBscore and the RadScore (0.02 ( p -value = 0.86)). The changes in the RLscore and the RadScore had a much stronger correlation of 0.22, which is statistically significant ( p -value = 0.02). This shows that the developed RadScore has the potential to be a quantitative monitoring tool for responses to therapy.

Subjects conceived through assisted reproductive technologies (ART) potentially suffer from impaired left ventricular (LV) function due to premature vascular aging. This study aimed to evaluate whether subtle differences in LV diastolic function can be observed echocardiographically between young ART subjects and their spontaneously conceived peers. The echocardiographic assessment included the measurement of LV dimensions, mitral inflow velocities, and myocardial velocity at early diastole (E', cm/s) at the LV wall and the interventricular septum (IVS). An average from E/E'LV and E/E'IVS (E/E'AVG) was derived. In total, 66 ART subjects and 83 controls (12.85 ± 5.80 years vs. 13.25 ± 5.89 years, p = 0.677) were included. The ART subjects demonstrated a significantly lower E'LV (19.29 ± 3.29 cm/s vs. 20.67 ± 3.78 cm/s, p = 0.020) compared to their spontaneously conceived peers. Study participants of ≥ 10 years of age displayed a significantly higher E/E'AVG (6.50 ± 0.97 vs. 6.05 ± 0.99, p = 0.035) within the ART cohort. The results of this study demonstrate a significantly lower LV diastolic function in the ART subjects. However, no significant changes in LV diastolic function were observed between the two groups when the results were adjusted for age, birth weight percentile, and gestational age. Those ART subjects born preterm might have an elevated risk of developing LV diastolic alterations and could therefore profit from close echocardiographic monitoring.

Multiple studies reported signs of vascular dysfunction in subjects conceived through assisted reproductive technologies (ART). The assessment of arterial stiffness in this cohort seems beneficial for risk stratification. Regional arterial stiffness of the abdominal aorta (AAO) and the common carotid arteries (CCA) was evaluated sonographically using two-dimensional speckle tracking in subjects conceived through ART and spontaneously conceived peers. Global arterial stiffness was assessed utilizing an oscillometric blood pressure device. The cohorts of 67 ART subjects and 86 spontaneously conceived peers (11.31 (8.10-18.20) years vs. 11.85 (8.72-18.27) years, p = 0.43) did not differ significantly in parameters of regional and global arterial stiffness. In the sub-analysis of study participants ≥10 years of age, markers of arterial stiffness did not display significant differences between both groups. However, a higher tendency of brachial systolic blood pressure was demonstrated in the ART cohort compared to the control group (120.18 ± 9.57 mmHg vs. 116.55 ± 8.05 mmHg, p = 0.050). The present study displayed no significant differences in arterial stiffness between ART subjects and spontaneously conceived peers. Moreover, this study suggests that arterial stiffness does not elevate more profoundly in ART subjects with increasing age. Further studies are required for a more detailed cardiovascular risk stratification of the ART cohort.

Background/Aims: Controversy exists regarding 3- or 4 drug antituberculosis therapy (conventional ATT) in uveitis patients having latent tuberculosis (LTB), especially while initiating therapy with corticosteroids and/or other immunosuppressants. Methods: We performed a monocentral retrospective analysis of posterior uveitis patients with latent TB. Latent TB was diagnosed, in case of a positive QuantiFERON®-TB-Gold test and normal chest imaging, after ruling out other causes of infectious and noninfectious uveitis. Patients with active TB were excluded. From 2016 to 2020 we included 17 patients. Ophthalmological evaluation consisted of Best corrected visual acuity (BCVA), slit lamp examination, fundoscopy, OCT, and fluorescein- and indocyaningreen- angiography before and at months 3, 6, 12, 24, and the last follow-up after treatment. Results: Initially, all patients had active posterior uveitis with occlusive (n = 5 patients) and nonocclusive retinal vasculitis (n = 12 patients). Mean follow up was 28 ± 15 months. Therapy was started with systemic corticosteroids (mean prednisolone equivalent 71.3 mg/d) and already after 3 months it could be tapered to a mean maintenance dosage of 8.63 mg/d. Additional immunosuppressive treatment with cs- or bDMARDs was initiated in 14 patients (82%) due to recurrences of uveitis while tapering the corticosteroids <10 mg per/day or because of severe inflammation at the initial visit. While being on immunosuppression, best corrected visual acuity increased from 0.56 logMAR to 0.32 logMAR during follow-up and only three patients had one uveitis relapse, which was followed by switch of immunosuppressive treatment. As recommended, TB prophylaxis with 300 mg/d isoniazid was administered in 11 patients for at least 9 months while being on TNF-alpha-blocking agents. No patient developed active tuberculosis during immunosuppressive therapy. Conclusion: Mainly conventional ATT is strongly recommended—as monotherapy or in combination with immunosuppressives—for effective treatment in patients with uveitis due to latent TB. Although in our patient group no conventional ATT was initiated, immunosuppression alone occurred as an efficient treatment. Nevertheless, due to possible activation of TB, isoniazid prophylaxis is mandatory in latent TB patients while being on TNF-alpha blocking agents.

Adolescents are the main consumer group of energy drinks (ED). Studies suggest that acute ED consumption is associated with increased peripheral blood pressure. Little is known of the ED-induced effects on arterial stiffness. Therefore, this study aimed to investigate the acute effects of ED consumption on arterial stiffness in healthy children and teenagers by conducting a prospective, randomized, single-blind, placebo-controlled, crossover clinical trial. Study participants ( n = 27, mean age = 14.53 years) consumed a body-weight-adjusted amount of an ED or a placebo on two consecutive days. Arterial stiffness was evaluated sonographically by two-dimensional speckle tracking of the common carotid artery (CCA) at baseline and up to four hours after beverage consumption. The ED intake led to a significantly decreased peak circumferential strain of the CCA (11.78 ± 2.70% vs. 12.29 ± 2.68%, p = 0.043) compared with the placebo. The results of this study indicate that the acute ED consumption might be associated with increased arterial stiffness in healthy children and teenagers. Minors, particularly those with increased cardiovascular morbidity, should be discouraged from ED consumption.

Background: This study aimed to investigate whether the cardiovascular care of Turner Syndrome (TS) women in Germany is in accordance with the latest clinical practice guidelines established by the 2016 Cincinnati international TS meeting., Methods: An anonymous online questionnaire was created to ask TS subjects about existing cardiovascular conditions and cardiovascular care received. Depending on cardiovascular morbidity and type of medical care received, the fulfillment of the latest clinical practice guidelines for the care of TS women was assessed., Results: 120 TS patients were included in this study. The mean age of TS subjects was 36.79 years. Only 80% of subjects received annual blood pressure measurements within the TS cohort, and only 60% received cardiac imaging according to international clinical practice guidelines. More than 55% of TS women did not feel well informed about TS-specific cardiovascular risk factors by their treating physician., Conclusions: A potential lack of cardiovascular care might be present in TS women in Germany as the results of this online patient survey suggest. The cardiovascular care of TS patients, particularly cardiac imaging and patient education, needs to receive more attention.

Severe respiratory syndrome coronavirus-2 (SARS-CoV-2) is a highly contagious beta-class coronavirus. Although vaccinations have shown high efficacy, the emergence of novel variants of concern (VOCs) has already exhibited traits of immune evasion. Thus, the development of tailored antiviral medications for patients with incomplete, inefficient, or non-existent immunization, is essential. The attachment of viral surface proteins to the cell surface is the first crucial step in the viral replication cycle, which for SARS-CoV-2 is mediated by the high affinity interaction of the viral trimeric spike with the host cell surface-located human angiotensin converting enzyme-2 (hACE2). Here, we used a novel and efficient next generation sequencing (NGS) supported phage display strategy for the selection of a set of SARS-CoV-2 receptor binding domain (RBD)-targeting peptide ligands that bind to the target protein with low µM to nM dissociation constants. Compound CVRBDL-3 inhibits the SARS-CoV-2 spike protein association to hACE2 in a concentration-dependent manner for pre- as well as post-complex formation conditions. Further rational optimization yielded a CVRBDL-3 based divalent compound, which demonstrated inhibitory efficacy with an IC 50 value of 47 nM. The obtained compounds were not only efficient for the different spike constructs from the originally isolated "wt" SARS-CoV-2, but also for B.1.1.7 mutant trimeric spike protein. Our work demonstrates that phage display-derived peptide ligands are potential fusion inhibitors of viral cell entry. Moreover, we show that rational optimization of a combination of peptide sequences is a potential strategy in the further development of therapeutics for the treatment of acute COVID-19.

Turner syndrome (TS) is a rare chromosomal disease with increased cardiovascular morbidity and mortality. The aim of this study was to investigate the influence of physical activity and diet quality on cardiovascular morbidity in German TS women. An anonymous online questionnaire was established. The questionnaire was based on the 2020 WHO recommendations on physical activity and sedentary behaviour and included the 14-Item Mediterranean Diet Assessment Tool. In addition, TS patients were asked about existing cardiovascular conditions. In total, 83 TS women were included in the final analysis. The achievement of <600 Metabolic Equivalent-minutes per week for recreational activities was significantly associated with the presence of arterial hypertension ( p = 0.006). High adherence to the Mediterranean diet was achieved by only 20.5% of TS subjects and tended to be inversely associated with the presence of lipid metabolism disorders ( p = 0.063). Only 37.3% of TS participants received nutritional counselling. Given the increased cardiovascular risk, specific counselling for lifestyle optimisation may play an important role in the management of TS. Further studies are required to evaluate the effects of regular aerobic physical training and different nutritional programs on cardiovascular morbidity in TS.

The objective of this study was to explore the mechanism of Hedyotis diffusa (HD) in mediating the detoxification of aflatoxin B 1 (AFB 1 )-induced hepatic injury in chicks. A total of 144 one-day-old male broilers (Cobb 500) were randomly assigned to four treatment groups ( n = 6 cages/diet, 6 chicks/cage). After three days of acclimation, the broilers were fed either a control diet (Control), Control plus 0.5 mg/kg of AFB 1 , or Control plus 0.5 mg/kg AFB 1 with 500 or 1000 mg/kg HD for two weeks. Both serum and liver were collected at the end of the feeding trial for biochemistry, histology, and NF-E2-related nuclear factor 2 (NRF2)/antioxidant response element (ARE) signaling analysis. Compared with Control, the AFB 1 treatment caused liver injury and decreased ( p < 0.05) body weight gain, feed intake, feed conversion ratio, and serum albumin and total protein by 6.2-20.7%. AFB 1 also induced swelling, necrosis, and severe vacuolar degeneration in chicks' livers. Notably, HD supplementation at 500 and 1000 mg/kg mitigated ( p < 0.05) the alterations induced by AFB 1 . HD supplementation alleviated ( p < 0.05) AFB 1 -induced impairment in hepatic glutathione peroxidase activity, protein carbonyl, and exo-AFB 1 -8,9-epoxide (AFBO)-DNA concentrations by 57.7-100% and increased ( p < 0.05) the activities of superoxide dismutase and catalase by 23.1-40.9% more than those of AFB 1 treatment alone. Furthermore, HD supplementation at the two doses upregulated ( p < 0.05) NRF2, NAD(P)H: quinone oxidoreductase-1, heme oxygenase-1, glutathione cysteine ligase catalytic subunit, and glutathione-S transferase A2 and A3 in livers relative to the AFB 1 group by 0.99-3.4-fold. Overall, dietary supplementation of HD at a high dose displayed better protection effects against aflatoxicosis. In conclusion, a dietary HD supplementation at 500 and 1000 mg/kg protected broilers from AFB 1 -induced hepatotoxicity, potentially due to the activation of NRF2/ARE signaling in the chicks.

Circadian rhythm gene expression in cerebral pacemaker regions is regulated by a transcriptional-translational feedback loop across the 24-h day-night cycle. In preclinical models of subarachnoid hemorrhage (SAH), cyclic gene expression is disrupted. Stabilization of circadian rhythm gene expression attenuates susceptibility to ischemic damage in both neuronal and myocardial tissues. In this clinical observational study, circadian rhythm gene Period-2 ( Per2 ) mRNA expression levels were determined from blood leukocytes and cerebrospinal fluid (CSF) cells via real-time PCR on days 1, 7 and 14 after aneurysm rupture in 49 patients with spontaneous SAH. CSF Per2 expression was markedly suppressed immediately after SAH and remained suppressed over the course of two weeks of ICU treatment. Short-term mortality as well as occurrence of delirium was associated with greater extent of Per2 suppression on day 1 after SAH. Patients that developed delayed cerebral ischemia exhibited comparatively lower Per2 expression levels on day 7 after SAH, while presence of vasospasm remained unaffected. However, Per2 expression did not differ in patient groups with favourable or non-favourable functional neurological outcome (modified Rankin Scales 1-3 vs. 4-6). While our findings suggest a potential protective effect of stable circadian rhythm gene expression on the extent of ischemic damage, this effect was confined to the early disease course and was not reflected in patients' functional neurological outcome.

(1) Background: A detailed understanding of the pathophysiology of hemorrhagic stroke is still missing. We hypothesized that expression of heme oxygenase-1 (HO-1) in microglia functions as a protective signaling pathway. (2) Methods: Hippocampal HT22 neuronal cells were exposed to heme-containing blood components and cell death was determined. We evaluated HO-1-induction and cytokine release by wildtype compared to tissue-specific HO-1-deficient ( LyzM-Cre.Hmox1 fl/fl ) primary microglia (PMG). In a study involving 46 patients with subarachnoid hemorrhage (SAH), relative HO-1 mRNA level in the cerebrospinal fluid were correlated with hematoma size and functional outcome. (3) Results: Neuronal cell death was induced by exposure to whole blood and hemoglobin. HO-1 was induced in microglia following blood exposure. Neuronal cells were protected from cell death by microglia cell medium conditioned with blood. This was associated with a HO-1-dependent increase in monocyte chemotactic protein-1 (MCP-1) production. HO-1 mRNA level in the cerebrospinal fluid of SAH-patients correlated positively with hematoma size. High HO-1 mRNA level in relation to hematoma size were associated with improved functional outcome at hospital discharge. (4) Conclusions: Microglial HO-1 induction with endogenous CO production functions as a crucial signaling pathway in blood-induced inflammation, determining microglial MCP-1 production and the extent of neuronal cell death. These results give further insight into the pathophysiology of neuronal damage after SAH and the function of HO-1 in humans.